What is the treatment for Clostridioides difficile (C. diff)-induced diarrhea?

Treatment of Clostridioides difficile Infection

For an initial episode of C. difficile infection, oral vancomycin 125 mg four times daily for 10 days or oral fidaxomicin 200 mg twice daily for 10 days are the first-line treatments, regardless of severity. 1

Initial Episode Treatment Algorithm

Non-Severe CDI (First-Line Options)

• Oral vancomycin 125 mg four times daily for 10 days 2, 1
• Oral fidaxomicin 200 mg twice daily for 10 days 2, 1
• Metronidazole 500 mg three times daily for 10 days is no longer recommended as first-line therapy due to lower clinical success rates and increasing treatment failures 1, 3
• Metronidazole may only be considered when access to vancomycin or fidaxomicin is limited, and should be restricted to initial episodes of mild-moderate CDI 2, 1

Severity criteria for non-severe CDI: WBC ≤15,000 cells/mL, serum creatinine <1.5 mg/dL, stool frequency <4 times daily, no signs of severe colitis 1

Severe CDI

• Oral vancomycin 125 mg four times daily for 10-14 days 2, 1
• Vancomycin is superior to metronidazole in severe disease 2

Severity criteria for severe CDI: WBC ≥15,000 cells/mL, serum creatinine >1.5 mg/dL, fever, rigors, hemodynamic instability, signs of peritonitis or ileus 1

Fulminant CDI (with ileus or toxic megacolon)

• Oral vancomycin 500 mg four times daily 2, 1, 4
• PLUS intravenous metronidazole 500 mg every 8 hours 2, 4
• PLUS rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema if ileus is present 2, 1, 4
• Early surgical consultation is essential 4

Recurrent CDI Treatment

First Recurrence

• Oral vancomycin in a tapered and pulsed regimen (e.g., 125 mg four times daily for 10-14 days, then twice daily for a week, once daily for a week, then every 2-3 days for 2-8 weeks) 2
• OR oral fidaxomicin 200 mg twice daily for 10 days if vancomycin was used for the initial episode 2
• OR standard vancomycin course if metronidazole was used initially 2

Second or Subsequent Recurrence

• Vancomycin in a tapered and pulsed regimen 2
• OR vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 2
• OR fidaxomicin 200 mg twice daily for 10 days 2
• OR fecal microbiota transplantation (FMT) after at least 2 recurrences (3 total CDI episodes) 2

Fecal Microbiota Transplantation

FMT is strongly recommended for patients with multiple recurrences who have failed appropriate antibiotic treatments. 2

• FMT has cure rates of 80-100% when administered via the colon 2
• The landmark randomized trial by van Nood showed 81% sustained resolution after FMT versus 27% with vancomycin alone (P <0.001) 2
• FMT efficacy increases with repeated administrations: approximately 50% for one FMT, 75% for two, and 90% for more than two 2
• FMT appears safe in the short term with mostly self-limited adverse events 2

Critical Supportive Measures

Discontinue Inciting Antibiotics

• Stop the offending antibiotic as soon as possible to reduce risk of recurrence 2, 1
• If continued antibiotic therapy is required, use agents less frequently associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 2

Avoid Antimotility Agents

• Do not use loperamide or opiates, especially in acute settings, as they may worsen outcomes 1

Infection Control

• Hand hygiene with soap and water is most effective for removing C. difficile spores; alcohol-based sanitizers do not kill spores 2
• Contact precautions and environmental disinfection are essential 2

Common Pitfalls

• Do not use metronidazole as first-line therapy for initial CDI episodes; vancomycin and fidaxomicin have superior outcomes 1, 3
• Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1
• Do not perform "test of cure" after CDI treatment 2
• Do not test asymptomatic patients as laboratory tests cannot distinguish colonization from infection 2
• Patients receiving metronidazole may have delayed response; consider extending treatment to 14 days if needed 2
• Factors predicting metronidazole failure include age >60 years, fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, and abnormal abdominal CT 1

Pediatric Considerations

For children with initial episode or first recurrence of non-severe CDI:

• Metronidazole 7.5 mg/kg/dose three or four times daily (max 500 mg per dose) for 10 days 2
• OR vancomycin 10 mg/kg/dose four times daily (max 125 mg per dose) for 10 days 2